In the past year this laboratory has studied the membrane receptors for norepinephrine in brain. We used (3H) dihydroalprenolol (DHA) to study beta-adrenergic receptor binding in rat brain. DHA binding appeared to be synaptic in a subcellular fractionation study of brain homogenates on linear sucrose density gradients and was not present in guinea pig cortex, a brain region lacking beta-adrenergic receptor physiological responses. We found that brain beta-adrenergic membrane receptors appear capable of the same rapid changes described for peripheral tissues. These findings suggest that DHA binds to beta-adrenergic receptors in brain and that these receptor binding sites are capable of rapid and reversible changes. We studied the alpha-adrenergic receptor in brain with two ligands, (3H) dihydroergocryptine (DHE) and (3H) WB 4101 (WB). The binding of both ligands in brain had some but not all the properties expected for alpha-adrenergic receptors. We therefore studied DHE binding in a model alpha-adrenergic receptor system, rat parotid acinar cells. In these cells, DHE binding exactly matched the physiological alpha-adrenergic response, K ion release. The alpha-receptor response in these parotid acinar cells rapidly desensitized and the desensitization was accompanied by rapid changes in DHE binding sites. This is the first demonstration of alpha-adrenergic desensitization and suggests that this receptor, like the beta-adrenergic and nicotinic cholinergic receptors, is capable of rapid, reversible changes. We plan to use the parotid system to find an appropriate ligand for measuring brain binding. We view the adrenergic neuron in brain as a model for all neurons and hope to characterize alterations in this neuron during hypoxia. The newly developed techniques for receptor measurements in brain offer a unique and exciting tool for such a study. The data generated by the present studies serve as a basis for a better understanding of complex cerebral function such as memory, learning, habituation, and drug withdrawal and may have implications for the treatment of stroke.